1. Field of the Invention
This invention relates in general to cardiac conduction defects in the heart. More particularly, it relates to a method of treating cardiac conduction defects by treating occlusions (both partial and total) in the arteries supplying blood to the specialized cardiac conduction cells of the heart. The specialized cardiac cells play an active role in controlling the cardiac cycle by receiving electrical impulses and conducting them throughout the heart. The cardiac cells are generally found in the conduction nodes, the conducting fibers that connect the conduction nodes, and portions of the myocardium muscle layer of the heart.
The term "occlusion" as used throughout this disclosure is intended to refer to both partial and total occlusions.
2. General Description of the Art
The cardiovascular system, also known as the blood-vascular system, generally includes the heart, a tortuous network of blood vessels and the blood flowing therein. The heart is a hollow muscle that functions as the central organ of the entire cardiovascular system. FIG. 1 illustrates the three layers that make up the walls of a normal human heart. One layer is the epicardium which is the layer of serous pericardium on the surface of the heart. The second layer is the myocardium which is a thick contractile middle layer having specially constructed and arranged cardiac cells and muscle cells. The third layer is the endocardium which includes the endothelial lining membrane connected to a connective tissue bed.
The heart pumps blood through the vascular system by periodically contracting and relaxing. FIG. 2 is a diagram illustrating how blood circulates throughout the human body through a network of tubes known generally as arteries, capillaries and veins. The arteries end in very minute vessels known as arterioles which open into the microscopic capillaries. After the blood has passed through the capillaries, it is collected into a series of larger vessels know as veins, and the veins return the blood to the heart. The terms "blood circulation" are generally used to describe how the blood moves through the heart and the above-described blood vessels.
FIG. 2 also illustrates a diagrammatic representation of the human heart 20. As shown in FIG. 2, the heart 20 is divided by a septum wall 22 into right and left halves, and each half is further divided into upper and lower cavities. The upper cavities are referred to as auricles or atria, and the lower cavities are referred to as ventricles. Thus, the heart 20 is divided into four cavities known generally as the right atrium 24, the left atrium 26, the right ventricle 28, and the left ventricle 30. In general, the right half of the heart contains venous or impure blood 32, and the left half of the heart contains arterial or pure blood 34.
The diagrammatic representation of the heart 20 shown in FIG. 2 is illustrated in further detail in FIG. 3. FIG. 3 shows that the four cavities of the heart are further separated by one-way valves which shutoff blood flow when they are closed and allow blood to flow in one direction when they are open. The right atrium 24 is separated from the right ventricle 28 by the tricuspid valve 36, and the left atrium 26 is separated from the left ventricle 30 by the mitral valve 38. The right ventricle 28 is separated from the pulmonary aorta by the pulmonary semilunar valve 40, and the left ventricle 30 is separated from the systemic aorta by the aortic semilunar valve 42.
Referring again to FIGS. 2 and 3, the heart 20 pumps pure blood 34 from the left ventricle 30 into the systemic arteries which carry the blood to the systemic capillaries, the intestinal capillaries and the hepatic capillaries. As the pure blood 34 passes through the capillaries, it provides the surrounding body tissues with the materials they need for growth and nourishment. The primary material supplied is oxygen. At the same time, the pure blood 34 receives from the body tissues the waste products resulting from their metabolism. Accordingly, the pure arterial blood 34 changes to impure venous blood 32 as it flows through the capillaries. The impure blood 32 is collected by the veins of the body and returned to the right atrium 24. As best shown in FIG. 3, impure blood is supplied to the right atrium via the superior vena cava and the inferior vena cava. The superior vena cava returns blood from the upper half of the body, and the inferior vena cava returns blood from the lower half of the body.
The impure blood then passes through the right atrium 24 to the right ventricle 28 which pumps it to the lungs (not shown) via the pulmonary arteries and the pulmonary capillaries. In the lungs, the impure blood is cleansed and oxygenated and returned via the pulmonary veins to the left atrium 24 of the heart. The left atrium 24 passes the pure blood 32 to the left ventricle 30 which pumps it out to the systemic arteries to begin the circulation process again.
The cardiac cycle may be defined as a complete heartbeat consisting of contraction (systole) and relaxation (diastole) of the atria and the ventricles. FIG. 4 illustrates the pressure-volume loops for the right and left ventricles as the heart goes through a complete cardiac cycle. The area enclosed in the loop is a measure of the work done by the heart in ejecting blood. Diagrammatic representations of the heart during one cardiac cycle surround the loops and are linked by arrows with their appropriate position (in time) on the loop. The contracting portions of the heart are shaded.
In all vertebrates, the cardiac cycle can be divided into four phases. The first phase of the cardiac cycle is known as the filling phase or atrial systole. In the atrial systole phase, the tricuspid valve and the mitral valve are shut, and the atria are filling with blood. Ventricular pressure at the start of this phase is low and falling. When ventricular pressure falls below atrial pressure, the tricuspid and mitral valves open, and blood flows rapidly into the right and left ventricles. The end of the ventricular relaxation phase (diastole) is marked by the start of ventricular contraction (systole) which increases ventricular pressure and shuts the atrioventricular valves.
The second phase is known as isovolumetric contraction. In the isovolumetric phase, the pressure in the ventricles increases, but no ejection of fluid takes place. As shown in FIG. 4, the tricuspid valve 36, mitral valve 38, pulmonic valve 40 and aortic valve 42 are closed. The ventricular muscle contracts, developing tension, and the pressure of the contained blood in the ventricle increases. This phase generally represents the period between the start of ventricular contraction (systole) and the opening of the pulmonic and aortic valves.
The third phase of the cardiac cycle is known as ventricular ejection. During this phase, the pressure in the ventricles exceeds the pressure in the atria, thus forcing the pulmonic and aortic valves 40, 42 open and pumping blood into the pulmonary and systemic arteries. The amount of blood pumped by a single ventricle during ejection is known as the stroke volume, which is usually measured in milliliters. The cardiac output, typically measured in liters per minute, is a product of the stroke volume multiplied by the heart rate. Normal cardiac output is approximately 4 to 8 liters per minute.
The fourth and final phase of the cardiac cycle is known as isovolumetric ventricular relaxation. During this phase, all inflow and outflow heart valves are closed, and ventricular pressure falls rapidly as the ventricular muscles relax. Some subatmospheric pressure can occur in this phase due to "elastic recoil" of the ventricle walls.
The heartbeat results from the development and organized control of ionic current flow through the specialized cardiac cells of the heart. This organized current flow allows the heart to pump blood by initiating the cyclical contraction and relaxation of the myocardial muscles surrounding the atria and ventricles of the heart. This organized current flow corresponds to the muscle contractions and relaxations of the cardiac cycle.
The specialized cardiac cells are generally found in the conduction nodes, the conducting fibers that connect the conduction nodes, and portions of the myocardial muscle layer of the heart. The cardiac conduction cells generally go through two electrical processes known as depolarization and repolarization. During depolarization, the cells are stimulated and the myocardium contracts. During repolarization, the myocardium relaxes.
FIG. 5 illustrates the specialized conduction system of the heart. The heart's conduction system stimulates and coordinates muscle contractions by conducting electrical impulses through the heart. The electrical impulses originate in the autonomic nervous system, and travel first to the sinoatrial (SA) node located in the right atrium 24. The sinoatrial node is referred to as the heart's "pacemaker" because it triggers and coordinates the electrical impulses that are sent throughout the heart.
Impulses from the sinoatrial node are initially sent to the right and left atria 24, 26 through the internodal tracts. The sinoatrial node normally fires between 60 and 100 times per minute. After the right and left atria 24, 26 have been stimulated, the impulse travels to the atrioventricular node which is located in the right atrium 24 near the tricuspid valve 36. The atrioventricular node delays the impulse, thus allowing the ventricles 28, 30, which are in diastole, to fill with blood. The impulse then continues to the bundle of His, which is a thick bundle of fibers extending down the septum wall 22, and spreads to the right and left bundle branches. The impulse continues from the right and left bundle branches to the Purkinje fibers, which spread throughout the inner surface of the right and left ventricles 28, 30.
Additional details about the heart and the cardiac conduction system may be found in the following publications: Gray's Anatomy by Henry Gray, F.R.S., published 1974 by Running Press, Philadelphia Pa.; Dorland's Illustrated Medical Dictionary, 25th Edition, published 1974 by W. B. Saunders, Philadelphia-London-Toronto; and McGraw-Hill Encyclopedia of Science & Technology, 6th Edition, Volume 3, pages 229 to 261. The entire disclosure of each of the above-identified references is incorporated herein by reference.
Cardiac conduction defects arise when the cardiac conduction system fails to sufficiently develop, control or transmit ionic current through the specialized cardiac cells of the heart. For example, bradycardia is a conduction defect that results in a slow or intermittently slow heartbeat. Bradycardia is considered clinically significant when the heart rate falls below about 60 beats per minute. Bradycardia may occur congenitally, or it may originate in the sinoatrial node, the atrioventricular node or the bundle of His.
Another type of cardiac conduction defect is tachycardia. In general, tachycardia is characterized by an excessively rapid heart rate. Tachycardia is considered clinically significant when the heart rate exceeds about 100 beats per minute. There are several forms of tachycardia, ranging in seriousness from inconvenient to life threatening. Some forms of tachycardia have origins in the upper cavities of the heart (supra ventricular tachycardia), while others originate from accessory pathways alongside the atrioventricular node (e.g. Wolf-Parkinson-White syndrome). Tachycardia may result in circus rhythms within the ventricle, and also uni-directional block phenomena within the atrioventricular node.
In general, atrial tachycardia is less serious because the remainder of the heart is usually unable to follow the very high triggering rhythms. Atrial tachycardia may be further mitigated because it is often accompanied by various degrees of atrioventricular block which reduces the ventricular rate to a more tolerable level. In any event, atrial tachycardia reduces cardiac output and causes shortness of breath, reduced stamina, and other ailments.
Ventricular tachycardia is characterized by severe reduction in the cardiac output and may result in periodic unconsciousness. There is also a significant potential for ventricular tachycardia to degrade to ventricular fibrillation with fatal results.
The currently used methods of treating cardiac conduction defects have focused primarily on treating the symptoms. Bradycardia is typically treated by providing electrical stimulation to the heart using an implanted or external pacemaker device. The pacemaker generally takes control of the triggering functions of the heart to increase the heart rate to a more normal level (about 70 beats per minute). Of course, the surgical procedure for connecting a pacemaker to the heart is invasive, and the pacemaker device requires periodic and expensive professional observation and maintenance. Atrial tachycardia is usually treated using drugs, surgery or an implantable pacemaker/cardioverter/defibrillator. These treatments have varying degrees of effectiveness, depending on the patient and the specific form of tachycardia. However, it is estimated that approximately 20% of all atrial tachycardia patients are refractory to the commonly used drug treatments. Ventricular tachycardia is typically treated with implantable cardioverters/defibrillators which have the same general drawbacks as pacemaker devices.
Thus, known methods of alleviating bradycardia and tachycardia conduction defects have focused primarily on prescribing treatments for the symptoms, rather than attacking the potential causes. Such causes have been ascribed to developing fibrosis, sequelae to myocardial infarction, ischemia and congestive heart failure, as well as some congenital causes. See, for example, Disorders of Atrioventricular Conduction in Acute Myocardial Infarction, Cardiology Clinics, Vol. 2, No. 1, February 1984, pages 29-34, by Jerry C. Griffin, M.D.; Arrhythmias in Acute Myocardial Infarction, Medical Clinics of North Americas Vol. 68 No. 4, July 1984, pages 1001-1008, by Galen S. Wagner, M.D.. However, these causes of cardiac conduction defect have not been discussed as reversible phenomena.
Thus, there is a need for a method of treating cardiac conduction defects that overcomes the expense, invasiveness, physical and psychological traumas, ineffectiveness, and other shortcomings of known methods of treatment.
Congestive heart failure occurs generally when significant regions of the heart becomes stiff and inflexible such that it looses some of its ability to properly contract, thereby reducing the cardiac output to clinically significant levels. Congestive heart failure has been generally attributed to a number of conditions such as heart valve malfunction. However, there is no obvious cause of congestive heart failure. Thus, there is a need for a method of treating congestive heart failure.
It is hereby noted that the descriptions of the art provided in this disclosure are not intended to constitute an admission that any patent, publication or other information referred to herein qualifies as "prior art" within the meaning of 35 .sctn. 102. Also, in accord with 37 CFR .sctn. 1.97, these descriptions shall not be construed to mean that: 1) a search has been made; 2) Applicant(s) consider(s) the information discussed herein to be "material" as defined in 37 CFR .sctn. 1.97; or 3) no other material information exists.